The APOBECS's (A3G, ASF and possibly A3H) are cellular DNA cytosine deaminases that are key innate anti-viral agents, particularly in response to HIV-1. Although the structures of the catalytic domains of these important enzymes are beginning to be elucidated, the details of their specificities and interactions with other cellular and viral macromolecules still remains to be determined. In this proposal we are using a combination of crystallographic, molecular modelling, calorimetry, mass spectrometry and viral studies to characterize the domains of these various APOBEC3's, both intra-moleculariy within their domains and intermoleculariy with their interactions with HIV-1 Vif.